Major depressive disorder in women is a significant health concern. Rates of depression in women are approximately twice those seen in men. Observations of gender-based differences in prevalence, presentation, and treatment response in depression raise questions about the underlying causes of such differences. In addition, the specific factors that predict vulnerability to reproductive-associated mood disturbance, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal mood disturbance, remain to be delineated. While a growing amount of controlled data is emerging that describes response to treatment in women who suffer from these disorders, further investigation is needed to identify subgroups of women who are most at risk for depression and to define the most effective treatments for these patients.